HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------WARNINGS AND PRECAUTIONS----------------------- These highlights do not include all the information needed to use FASLODEX® safely and effectively. See full prescribing information • Blood Disorders: Should be used with caution in patients with for FASLODEX. bleeding diatheses, thrombocytopenia, or anticoagulant use. (5.1) FASLODEX® (fulvestrant) injection • Hepatic Impairment: A 250 mg dose is recommended in patients with moderate hepatic impairment (2.2, 5.2, 8.6) INITIAL US APPROVAL: 2002 • Pregnancy: Fetal harm can occur when administered to a pregnant woman. Women should be advised of the potential hazard to the ----------------------RECENT MAJOR CHANGES------------------------- fetus and to avoid becoming pregnant while receiving FASLODEX. (5.3) Dosage and Administration, Recommended Dose (2.1), 09/2010 Dosage and Administration, Dose Modification (2.2), 09/2010 --------------------------ADVERSE REACTIONS----------------------------- Dosage and Administration, Administration Technique (2.3), 09/2010 • The most common, clinically significant adverse reactions -----------------------INDICATIONS AND USAGE------------------------- occurring in ≥ 5% of patients receiving FASLODEX 500 mg were: injection site pain, nausea, bone pain, arthralgia, headache, back FASLODEX is an estrogen receptor antagonist indicated for the: pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, • Treatment of hormone receptor positive metastatic breast cancer in asthenia, musculoskeletal pain, cough, dyspnea, and constipation. postmenopausal women with disease progression following (6.1) antiestrogen therapy. • Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of -------------------DOSAGE AND ADMINISTRATION--------------------- FASLODEX patients and were not dose-dependent. • FASLODEX 500 mg should be administered intramuscularly into To report SUSPECTED ADVERSE REACTIONS, contact the buttocks slowly (1 - 2 minutes per injection) as two 5 mL AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or injections, one in each buttock, on days 1, 15, 29 and once monthly www.fda.gov/medwatch for voluntary reporting of adverse thereafter. (2.1, 14) reactions • A dose of 250 mg is recommended in patients with moderate -------------------------DRUG INTERACTIONS------------------------------ hepatic impairment to be administered intramuscularly into the buttock slowly (1 - 2 minutes) as one 5 mL injection on days 1, 15, 29 and once monthly thereafter. (2.2, 5.2, 8.6) • There are no known drug-drug interactions. (7) -----------------DOSAGE FORMS AND STRENGTHS-------------------- -------------------USE IN SPECIFIC POPULATIONS---------------------- FASLODEX, an injection for intramuscular administration, is supplied • Nursing Mothers: discontinue drug or nursing taking into account as 50 mg/mL fulvestrant. (3) the importance of drug to the mother. (8.3) • Pediatric Patients: efficacy has not been demonstrated in girls with ------------------------CONTRAINDICATIONS------------------------------ McCune-Albright Syndrome and progressive precocious puberty. • Hypersensitivity (4) (8.4) SEE 17 FOR PATIENT COUNSELING INFORMATION AND FDA-APPROVED PATIENT LABELING Revised: 07/2011 FULL PRESCRIBING INFORMATION: CONTENTS* 8.3 Nursing Mothers 1 INDICATIONS AND USAGE 8.4 Pediatric Use 2 DOSAGE AND ADMINISTRATION 8.5 Geriatric Use 2.1 Recommended Dose 8.6 Hepatic Impairment 2.2 Dose Modification 8.7 Renal Impairment 2.3 Administration Technique 10 OVERDOSAGE 3 DOSAGE FORMS AND STRENGTHS 11 DESCRIPTION 4 CONTRAINDICATIONS 12 CLINICAL PHARMACOLOGY 5 WARNINGS AND PRECAUTIONS 12.1 Mechanism of Action 5.1 Blood Disorders 12.2 Pharmacodynamics 5.2 Hepatic Impairment 12.3 Pharmacokinetics 5.3 Use in Pregnancy 13 NONCLINICAL TOXICOLOGY 6 ADVERSE REACTIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 6.1 Clinical Trials Experience 14 CLINICAL STUDIES 6.2 Post-Marketing Experience 16 HOW SUPPLIED/STORAGE AND HANDLING 7 DRUG INTERACTIONS 17 PATIENT COUNSELING INFORMATION 8 USE IN SPECIFIC POPULATIONS *Sections or subsections omitted from the full prescribing information are 8.1 Pregnancy not listed. Reference ID: 3014913 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE FASLODEX is indicated for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dose The recommended dose is 500 mg to be administered intramuscularly into the buttocks slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter [see Clinical Studies (14)]. 2.2 Dose Modification Hepatic Impairment: A dose of 250 mg is recommended for patients with moderate hepatic impairment (Child-Pugh class B) to be administered intramuscularly into the buttock slowly (1 - 2 minutes) as one 5 mL injection on days 1, 15, 29 and once monthly thereafter. FASLODEX has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C) [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)]. 2.3 Administration Technique The proper method of administration of FASLODEX for intramuscular use is described in the instructions that follow: 1. Remove glass syringe barrel from tray and check that it is not damaged. 2. Remove perforated patient record label from syringe. 3. Peel open the safety needle (SafetyGlide™) outer packaging. For complete SafetyGlide™ instructions refer below to the "Directions for Use of SafetyGlide™". 4. Break the seal of the white plastic cover on the syringe luer connector to remove the cover with the attached rubber tip cap (see Figure 1). 5. Twist to lock the needle to the luer connector. 6. Remove needle sheath. 7. Remove excess gas from the syringe (a small gas bubble may remain). 8. Administer intramuscularly slowly in the buttock. 9. Immediately activate needle protection device upon withdrawal from patient by pushing lever arm completely forward until needle tip is fully covered (see Figure 2). 2 Reference ID: 3014913 10. Visually confirm that the lever arm has fully advanced and the needle tip is covered. If unable to activate, discard immediately into an approved sharps collector. 11. Repeat steps 1 through 10 for second syringe. How To Use FASLODEX. For the 2 x 5 mL syringe package, the contents of both syringes must be injected to receive the 500 mg recommended dose. SAFETYGLIDE™ INSTRUCTIONS FROM BECTON DICKINSON SafetyGlide™ is a trademark of Becton Dickinson and Company Reorder number 305917 CAUTION CONCERNING SAFETYGLIDE™ Federal (USA) law restricts this device to sale by or on the order of a physician. To help avoid HIV (AIDS), HBV (Hepatitis), and other infectious diseases due to accidental needlesticks, contaminated needles should not be recapped or removed, unless there is no alternative or that such action is required by a specific medical procedure. WARNING CONCERNING SAFETYGLIDE™ Do not autoclave SafetyGlide™ Needle before use. Hands must remain behind the needle at all times during use and disposal. DIRECTIONS FOR USE OF SAFETYGLIDE™ For each syringe: Remove glass syringe barrel from tray and check that it is not damaged. Peel apart packaging of the SafetyGlide™, break the seal of the white plastic cover on the syringe Luer connector and attach the SafetyGlide™ needle to the Luer Lock of the syringe by twisting. Transport filled syringe to point of administration. Pull shield straight off needle to avoid damaging needle point. Administer injection following package instruction. 3 Reference ID: 3014913 For user convenience, the needle ‘bevel up’ position is orientated to the lever arm, as shown in Figure 3. Immediately activate needle protection device upon withdrawal from patient by pushing lever arm completely forward until needle tip is fully covered (Figure 2). Visually confirm that the lever arm has fully advanced and the needle tip is covered. If unable to activate, discard immediately into an approved sharps collector. Activation of the protective mechanism may cause minimal splatter of fluid that may remain on the needle after injection. For greatest safety, use a one-handed technique and activate away from self and others. After single use, discard in an approved sharps collector in accordance with applicable regulations and institutional policy. Becton Dickinson guarantees the contents of their unopened or undamaged packages to be sterile, non-toxic and non-pyrogenic. Figure 1 Figure 2 4 Reference ID: 3014913 Figure 3 3 DOSAGE FORMS AND STRENGTHS FASLODEX, an injection for intramuscular administration, is supplied as 5-mL prefilled syringes containing 50 mg/mL fulvestrant. 4 CONTRAINDICATIONS FASLODEX is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with FASLODEX. 5 WARNINGS AND PRECAUTIONS 5.1 Blood Disorders Because FASLODEX is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use. 5.2 Hepatic Impairment The safety and pharmacokinetics of FASLODEX were evaluated in a study in seven subjects with moderate hepatic impairment (Child-Pugh class B) and seven subjects with normal hepatic function. Exposure was increased in patients with moderate hepatic impairment, therefore a dose of 250 mg is recommended [see Dosage and Administration